Transfer of perfluoroalkyl substances from mother to fetus in a Spanish birth cohort
Introduction
Perfluoroalkyl substances (PFAS) are synthetic chemicals widely used in many industrial and commercial applications such as, the coating of paper and packaging, textiles and leather, fire-fighting foam, photography industry, cleaning products and, pesticides (Casals-Casas and Desvergne, 2011). The PFAS most studied are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) because of their widespread use, environmental persistence and, long biological half-lives (4–5 years) (Olsen et al., 2007). However, there are other PFAS (e.g. perfluorobutane sulfonate [PFBS], perfluorohexane sulfonate [PFHxS] and perfluorononanoate [PFNA]) that are less frequently studied, but their production and use is also widespread (Prevedouros et al., 2006). For example, PFBS is replacing PFOS (Oldham et al., 2012), and PFNA blood concentrations are increasing in the US NHANES population (Kato et al., 2011).
PFAS can cross the placental barrier (Fei et al., 2007, Midasch et al., 2007, Monroy et al., 2008). An increasing number of prospective studies have assessed the effects of prenatal PFAS exposure on a range of child health outcomes, measuring PFAS concentrations either in maternal or cord blood samples. For example, PFOA has been associated with a reduction in birth weight in a recent meta-analysis of nine studies (Johnson et al., 2014, Lam et al., 2014). Another review supports this conclusion (Bach et al., 2015), although more cautiously, because confounding by glomerular filtration rate cannot be excluded (Verner et al., 2015). For PFOS evidence is not consistent (Bach et al., 2015). Further, PFAS are suspected obesogens in experimental studies (La Merrill and Birnbaum, 2012), but there are few human studies and these show conflicting results with positive associations (Halldorsson et al., 2012, Høyer et al., 2015, Maisonet et al., 2012) and null associations (Andersen et al., 2013, Barry et al., 2014) on offspring body mass index (BMI) and weight at different ages. PFAS exposure may also be associated with decreased antibody response to childhood vaccines (Grandjean et al., 2012, Granum et al., 2013) and with childhood hypertension (Geiger et al., 2014). Studies evaluating associations between fetal exposure to PFAS and neurodevelopmental outcomes are inconsistent with several studies suggesting no association and only a few reporting adverse effects (Roth and Wilks, 2014).
PFAS fetal body burden may be best estimated in cord blood samples (Hanssen et al., 2010) because PFAS bind to serum albumin (Salvalaglio et al., 2010). However, many studies have used maternal blood during pregnancy as a surrogate; probably due to difficulties on cord blood collection or low availability of samples. Furthermore, many studies alternately used either maternal plasma or serum assuming that PFAS distribute evenly between both blood compartments (Fei et al., 2007, Hanssen et al., 2010, Monroy et al., 2008, Porpora et al., 2013). Only one study has studied the distribution of PFHxS, PFOS and PFOA between plasma and serum samples from the same subject and concluded that these PFAS distributed evenly in both blood compartments, but 78% of the subjects included were men (average age: 49 years) working in a fluorochemical factory (Ehresman et al., 2007). Understanding if PFAS have a similar distribution between plasma and serum during pregnancy could ease the comparison between studies.
Socio-demographic factors may determine PFAS concentrations in maternal and cord blood. Some studies indicate that higher PFAS levels are associated with older maternal age (Kato et al., 2014, Lien et al., 2013), lower parity and less previous breastfeeding (Ode et al., 2013), higher maternal education (Lien et al., 2013) and Asian maternal race (Apelberg et al., 2007b) but results are mainly for PFOS and PFOA and are still inconsistent (Ode et al., 2013). Moreover, evidence is limited on the maternal determinants that influence the PFAS transfer efficiency from the mother to the fetus.
In this study we aimed to evaluate PFAS transfer between mother and fetus and determine its predictors in a Spanish birth cohort. Our objectives were (1) to determine the concentrations of five PFAS (PFBS, PFHxS, PFOS, PFOA and PFNA) in maternal blood samples (plasma and serum) and in cord serum samples; (2) to evaluate the correlations and transfer ratio between PFAS concentrations matched maternal-cord samples and; (3) to evaluate which socio-demographic factors predict PFAS transfer from mother to fetus.
Section snippets
Study population
The Environment and Childhood Project (INMA) is a network of prospective population-based birth cohorts in Spain; aiming to understand the associations of pre and postnatal environmental exposures and child health (www.proyectoinma.org). Details on the recruitment and follow-up have been described elsewhere (Guxens et al., 2012). During 2003–2006 women from two Spanish regions (Sabadell and Valencia) were recruited in their first trimester of pregnancy (n=1484) and were followed-up until
Results
Women in our subsample were 32.1 (sd: 4.8) years of age on average, 42% were multiparous, 29% had university studies and, 26% consumed alcohol during pregnancy (Table 1). We did not detect PFBS in any of the samples so it was excluded from the analysis. PFHxS was detected in all but 2% and 4% of maternal plasma and serum samples, respectively and, 12% of cord serum samples. Whereas PFOS, PFOA and PFNA were detected in every maternal and cord sample. Table 2 describes PFAS concentrations. PFAS
Discussion
In this study we detected four different PFAS in maternal and fetal blood samples from a Spanish birth cohort. Our median PFAS concentrations in both maternal and fetal matrices tended to be higher than previous recent studies (Fromme et al., 2010, Hanssen et al., 2010, Porpora et al., 2013), but lower than studies conducted before 2003 (Fei et al., 2007, Midasch et al., 2007) (see Table 4). Differences in the year of sample collection should be considered when interpreting our results. Our
Conclusions
In this Spanish birth cohort we detected PFHxS, PFOS, PFOA and PFNA in maternal blood (serum and plasma) and cord serum samples with good correlations between maternal-cord matrices, confirming that PFAS transfer across the placenta. PFAS placental transfer was higher with increasing maternal age. Our study suggests that maternal plasma or serum samples collected early in pregnancy are good proxies to assess the fetal body burden of PFAS in epidemiological studies.
Conflict of interest statement
There is no conflict of interest in our study.
Funding sources and ethics
This study was funded in part by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), and from Spain: Instituto de Salud Carlos III and The Ministry of Health (Red INMA G03/176, CB06/02/0041, FIS-PI12/01890, FIS-PI041436, FIS- PI081151, FIS-PI06/0867, FIS-PS09/00090 FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647,, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, 14/00891, 14/01687, Miguel Servet 11/0178, and pre-doctoral
Acknowledgments
We would like to thank all the funding agencies for supporting our research. We would particularly like to thank all the participants for their generous collaboration. A full roster of the INMA Project Investigators can be found at: http://www.proyectoinma.org/presentacion-inma/listado-investigadores/en_listado-investigadores.html
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